Lipid Synthesis + Degradation Flashcards
(47 cards)
How are fats obtained?
from diet or made new from carbohydrates
Role of fats in biological functions?
Membranes
Uptake of lipid soluble vitamins
As precursors of steroid hormones
Energy store
Why is fat a vital store of energy?
The energy content of fat per gram is over twice that of either carbohydrate or protein 1g fat - 37kj 1g protein - 17kj 1g carbohydrate - 16kj
Health implications of fat?
- 40% of energy of British Diet from fat
- Adult obesity rose from 14.9% to 25.6% between 1993 and 2014
- Obesity BMI 30kg/m^2
- 30,000 premature deaths annually
- £4.2bn in 2007 + increased to 6.3bn in 2015
- 75% of will be obese within 15 years
- Government policy is to reduce this to <35%
- In 2016 :
62. 8% of adults overweight/obese
30. 3% of children overweight/obese
26. 1% of adults + 16% of children obese
What molecules affect lipid metabolism?
FA
Triglycerides or Neutral Fats
Cholesterol
How body uses fat?
- Calorific intake > consumption then excess –> fat
- Cardiac muscle use fats as preferred energy source
- Dietary carb most common source of metabolic building blocks although some AA can also be used
- Fats stored in adipose tissue but majority synthesised in liver
Structure of FA?
- Chains of methyl groups
- Terminal carboxyl group
- Double bonds in cis conformation
- Humans unable to create double bonds less than position 9
- Essential FA obtained from diet
Where does lipid synthesis occur?
cytosol of liver hepatocytes
Where does lipid degradation occur?
via beta oxidation in mitochondria of liver hepatocyte
Features of triglycerides?
-Neutral fats (how most fats are stored)
-3FA attached to a glycerol backbone
-glycerol made from glycolysis by glycerol-3-
phosphate
-glycerol fed into glycolysis
What does FA synthesis require?
ACoA
NADPH
ATP
-It involves sequential addition of 2 two C units derived from ACoA
What does transfer of ACoA to cytosol provide?
40% NADPH (60% additional NADPH from pentose phosphate pathway)
How liver makes FA?
-Cell wants to generate ATP
-ACoA feed into Krebs cycle
-ACoA + oxaloacetate
-forms citrate –> ETC
BUT in hepatocyte make FA for energy
-citrate transported out of mitochondria + remove ACoA
-ACoA makes FA +/ cholesterol
Fate of FA after made in liver?
-Remain in liver (liver lipids)
-Transported to peripheral tissue adipocytes for storage via:
exported bound within lipoproteins
bound to albumin as free FA
Describe transfer of ACoA to cytosol
-formation of citrate in mitochondria
-pumped into cytosol via citrate-malate antiport
-cyclical process as if mitochondria’s citrate removed then removing component of Krebs cycle (as we are
removing oxaloacetate as it is a cycle)
-citrate breaks down -> ACoA + oxaloacetate
-oxaloacetate -> malate
-malate -> pyruvate + NADH
-pyruvate transported into mitochondrion
-pyruvate -> oxaloacetate
What drives rate-limiting 1st step of FA synthesis?
Vital irreversible regulatory step + driven (activated)
in part by amount of citrate present (positive feed forward) as amount of citrate in a cell will rise when flow of glucose via glycolytic pathway increased
Note that the ACoA binds to a molecule that allows the reaction to occur, this
molecule is acyl carrier protein (ACP).
The reaction requires the vitamin biotin to work. The reaction requires ATP
What drives rate-limiting 1st step of FA synthesis?
Vital irreversible regulatory step + driven (activated)
in part by amount of citrate present (positive feed forward) as amount of citrate in a cell will rise when flow of glucose via glycolytic pathway increased
What inhibits rate-limiting 1st step of FA synthesis?
end product palmitate (negative feedback)
What inhibits rate-limiting 1st step of FA synthesis?
end product palmitic acid (negative feedback)
Equation for rate-limiting 1st step of FA synthesis?
ACoA (C3) + ATP + HCO3- -> malonylCoA (C2) + ADP + Pi
via Acetyl-CoA carboxylase
Equation for rate-limiting 1st step of FA synthesis?
ACoA (C2) + ATP + HCO3- -> malonylCoA (C3) + ADP + Pi
via Acetyl-CoA carboxylase
What’s expression of Acetyl-CoA carboxylase controlled by?
Increased by high carbohydrate + low fat
Decreased by low carbohydrate + high fat
Describe FA elongation
-rate-limiting step
-malonyl CoA + ACP
-forms malonyl-ACP (C3)
-2nd ACoA binds to ACP
-undergoes a condensation reaction with malonyl-ACP
-forms CO2 + Aceto-acetyl-ACP (C4)
-3 reactions : reduction, dehydration, another reduction coming out as butyryl-ACP (C4)
-butyryl ACP + malonyl-ACP - condensation
-forms 2nd CO2 , now
we have a 6-carbon molecule.
So this reaction allows addition of 2
carbon units each time in the form of
ACoA. The two reduction reactions
require NADPH, which we have
generated through the citrate-malate
transporting or the pentose-
phosphate pathway.
All the enzymes required for the
reactions above form a multi-functional
complex called Fatty acid synthase,
which exists as a dimer. By having a
multi-enzyme complex all the reactions
to occur are very close to each other
and the products of one reaction are
very close to the active site of the next
enzyme in the chain.
As the fatty acid chain is increased as the enzyme goes around and around in the
cycle (adding the carbons and doing the reductions and dehydrations etc.) above
until the chain reaches the required length and is released.
Describe FA elongation
- rate-limiting step
- malonylCoA + ACP -> malonyl-ACP (C3)
- 2nd ACoA + ACP -> acteyl-ACP (C2)
- acteyl-ACP + malonyl-ACP - condensation
- forms CO2 + aceto-acetyl-ACP (C4)
- 3 reactions : reduction, dehydration, another reduction coming out as butyryl-ACP (C4)
- butyryl ACP + malonyl-ACP - condensation
- forms 2nd CO2 + C6
- allows addition of 2 C units each time - ACoA
- 2 reductions require NADPH
- enzymes required form a multi-functional complex called FA synthase (dimer)
- multi-enzyme complex allows all reactions are close to each other + products of 1 reaction are close to active site of next enzyme in chain
